ArticleJournal of cancer research and clinical oncology2019
The efficacy of a coordinated pharmacological blockade in glioblastoma stem cells with nine repurposed drugs using the CUSP9 strategy.
Article in Journal of cancer research and clinical oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Effect of Disulfiram and Copper Plus Chemotherapy vs Chemotherapy Alone on Survival in Patients With Recurrent Glioblastoma: A Randomized Clinical Trial.JAMA network open · 2023Trial
- Drug resistant glioblastoma stem cells exhibit enriched stemness signatures and share extracellular matrix overexpression.BMC cancer · 2025Article
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- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
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- Potential Benefits of Adding Alendronate, Celecoxib, Itraconazole, Ramelteon, and Simvastatin to Endometrial Cancer Treatment: The EC5 Regimen.Current issues in molecular biology · 2025Article
- Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model.Neuroscience bulletin · 2024Article
- Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review.Experimental hematology & oncology · 2024Review
- A two-pronged approach against glioblastoma: drug repurposing and nanoformulation design for in situ-controlled release.Drug delivery and translational research · 2023Article
- Cancer Metastasis and Treatment Resistance: Mechanistic Insights and Therapeutic Targeting of Cancer Stem Cells and the Tumor Microenvironment.Biomedicines · 2022Review
- Precision oncology using ex vivo technology: a step towards individualised cancer care?Expert reviews in molecular medicine · 2022Review
- Updates in IDH-Wildtype Glioblastoma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Article
- Article
- Discovery of a New CaMKII-Targeted Synthetic Lethal Therapy against Glioblastoma Stem-like Cells.Cancers · 2022Article
- Glioblastoma and the search for non-hypothesis driven combination therapeutics in academia.Frontiers in oncology · 2022Review
- Disulfiram in glioma: Literature review of drug repurposing.Frontiers in pharmacology · 2022Review
- Nuclear size rectification: A potential new therapeutic approach to reduce metastasis in cancer.Frontiers in cell and developmental biology · 2022Review
- Drug Repurposing for Glioblastoma and Current Advances in Drug Delivery-A Comprehensive Review of the Literature.Biomolecules · 2021Review
- In Vitro and Clinical Compassionate Use Experiences with the Drug-Repurposing Approach CUSP9v3 in Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeConstructed from a theoretical framework, the coordinated undermining of survival paths in glioblastoma (GBM) is a combination of nine drugs approved for non-oncological indications (CUSP9; aprepitant, auranofin, captopril, celecoxib, disulfiram, itraconazole, minocycline, quetiapine, and sertraline) combined with temozolomide (TMZ). The availability of these drugs outside of specialized treatment centers has led patients to embark on combination treatments without systematic follow-up. However, no experimental data on efficacy using the CUSP9 strategy in GBM have been reported.
methodsUsing patient-derived glioblastoma stem cell (GSC) cultures from 15 GBM patients, we described stem cell properties of individual cultures, determined the dose-response relationships of the drugs in the CUSP9, and assessed the efficacy the CUSP9 combination with TMZ in concentrations clinically achievable. The efficacy was evaluated by cell viability, cytotoxicity, and sphere-forming assays in both primary and recurrent GSC cultures.
resultsWe found that CUSP9 with TMZ induced a combination effect compared to the drugs individually (p < 0.0001). Evaluated by cell viability and cytotoxicity, 50% of the GSC cultures displayed a high sensitivity to the drug combination. In clinical plasma concentrations, the effect of the CUSP9 with TMZ was superior to TMZ monotherapy (p < 0.001). The Wnt-signaling pathway has been shown important in GSC, and CUSP9 significantly reduces Wnt-activity.
conclusionsAdding experimental data to the theoretical rationale of CUSP9, our results demonstrate that the CUSP9 treatment strategy can induce a combination effect in both treatment-naïve and pretreated GSC cultures; however, predicting response in individual cultures will require further profiling of GSCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.